Defining the role of genes implicated in the control of cellular proliferation in human cancer requires both access to clinical specimens and to high throughput technologies for expression and mutational analyses. The objective of Core C (Molecular Pathology) is to provide an efficient strategy to screen genes identified by P01 investigators as regulators of cellular proliferation for their relevance in human cancer. The core will provide expertise in the assembly and genomic mapping of human and mouse orthologs of novel genes identified through genetic screens in model organisms. Rapid analysis of cell type-specific expression in mammalian tissues will be provided, using oligonucleotide-based RNA-in situ hybridization to panels of embryonic and adult mouse sections. Mutational analysis of new genes will be undertaken in both cancer-derived cell lines and primary human tumor specimens. Automated sequencing facilities and denaturing HPLC are available for the rapid detection of sequence variants in human and mouse tumors, germline specimens from high risk cancer pedigrees, and a cohort of healthy controls. The Molecular Pathology Core brings together expertise in mammalian pathology and genetics to facilitate the use of shared clinical materials and expertise and to maximize the allocation of resources. The core is under the direction of Dr. Stamenkovic, Chief of Molecular Pathology at MGH, who has extensive expertise in tissue expression studies. Dr. Bell, an expert in human genetics and mutational analysis strategies, will serve as Co-Director.